Related Experiment Video
Updated: Dec 11, 2025

Genome-wide Protein-protein Interaction Screening by Protein-fragment Complementation Assay PCA in Living Cells
Published on: March 3, 2015
A Human IgSF Cell-Surface Interactome Reveals a Complex Network of Protein-Protein Interactions
Woj M Wojtowicz1, Jost Vielmetter2, Ricardo A Fernandes1
1Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Researchers mapped over 380 novel cell-surface protein-protein interactions (PPIs), revealing a complex communication network. This discovery enhances understanding of immune and nervous system functions and identifies potential therapeutic targets.
Area of Science:
- Cell Biology
- Immunology
- Neuroscience
- Proteomics
Background:
- Cell-surface protein-protein interactions (PPIs) are crucial for cell-cell communication, recognition, and responses.
- Understanding these interactions is vital for deciphering biological processes and disease mechanisms.
Purpose of the Study:
- To systematically screen for novel human cell-surface and secreted protein-protein interactions (PPIs).
- To identify new interaction partners for both known and orphan receptors.
- To build a comprehensive interactome map of cell-surface proteins.
Main Methods:
- A high-throughput, automated ELISA-based screening platform was utilized.
- An interactome screen of 564 human cell-surface and secreted proteins, predominantly immunoglobulin superfamily (IgSF) proteins, was performed.
- Phylogenetic homology analysis, surface plasmon resonance, and cell binding assays were employed for validation.
Main Results:
- The screen identified approximately 380 previously unreported PPIs among 318,096 tested combinations.
- New interactions were found for receptors with known ligands and for "orphan" receptors.
- Identified PPIs involve proteins in diverse functions, including immune and nervous system development, metabolism, and reproduction.
Conclusions:
- A vast and intricate network of cell-surface PPIs has been uncovered.
- These novel interactions provide a valuable resource for investigating biological functions.
- The identified PPIs represent potential targets for therapeutic drug development.
Related Concept Videos
Protein-protein Interfaces
Protein-Protein Interfaces
Protein Networks
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
Protein Networks
Assembly of Signaling Complexes
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Protein Complexes with Interchangeable Parts
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...

